Adicet Bio Inc Aktie

Hello, everyone, and welcome to the Adicet webcast. [Operator Instructions]. This call is being recorded.

I'll now turn the call over to Chen Schor, CEO of Adicet Bio. Please go ahead.

Good morning, everyone, and welcome to today's conference call to discuss the data we announced this morning from our ongoing Phase I study of ADI-001 demonstrating very promising safety and efficacy results in patients with LN and SLE.

I'll start the presentation with a few remarks before turning it over to Dr. Julie Maltzman, our Chief Medical Officer, who will summarize the clinical data to date. After that, we'll be joined by Dr. Blake Aftab, our Chief Scientific Officer, to walk us through the data demonstrating clear evidence immune reset that we observed in the study. And then Nick Harvey, our Chief Financial Officer, will join us for Q&A. Next slide, please.

Before we start, please note that today's call may include forward-looking statements based on our current expectations. These statements represent our judgment as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed. Please refer to our filings with the Securities and Exchange Commission for more information.

And now without further delay, let's get started. We're excited to share with you that the key takeaway from the Phase I study we are sharing today points to potentially unequivocal success for patients with autoimmune diseases and for treating physicians.

We believe this data set highlights the potential of ADI-001 to become a transformational paradigm-changing approach to treating patients with autoimmune diseases. These preliminary data checked all the boxes in terms of the efficacy and safety results that we had hoped to see at this stage.

Let's take a moment to revisit our aspiration for this trial. Previously, we laid out what good readout from the trial would be. First, we said that the data would hopefully demonstrate favorable safety profile suitable for outpatient administration. We clearly have that, with no SAEs, no CRS events greater than Grade 1 and no ICANS. We believe this lays the groundwork for ADI-001, potential advantage of being used as an outpatient therapy and available to many patients with autoimmune diseases.

We also said we wanted to achieve remission or halt disease progression. And we did, as you will see in the clinical data we present today. All patients, which includes five LN patients and two SLE patients with a follow-up ranging from 2 to 9 months experienced rapid and sustained reductions in their SLEDAI-2K and Physician Global Assessment or PGA scores.

Next, we wanted to show preserved or immune kidney function with a complete renal response or CRR rate of at least 40%, which is what regulatory authorities signaled to other companies as the bar for success in single-arm pivotal studies with B-cell depleting cell therapies for the treatment of LN. And indeed, kidney function improved in all five LN patients, including three complete renal responses, which were also DORIS remissions and two partial renal responses. We also wanted to see immune reset and emergence of B-cell repertoire that will support a onetime therapy, and we clearly did, which Blake will present shortly.

We hope to see a discontinuation of immunosuppressants and discontinuation or reduction in the corticosteroid doses to physiological levels. That box was clearly checked.

Finally, we wanted to see the potential for ADI-001 to become an off-the-shelf therapy with no need for leukapheresis, and we have that as well.

In summary, with all these boxes checked, today's data are a clear win for LN and SLE patients. These data exceeded our expectations. The totality of the data suggests that ADI-001 has the potential to be an off-the-shelf onetime therapy available for autoimmune patients in an outpatient setting with an impressive efficacy profile and favorable safety. Such a profile may enable rapid execution of our clinical development plan and if ADI-001 is approved, significant commercial potential.

Given the data we're presenting today, we plan to request a meeting with the U.S. Food and Drug Administration, or FDA, in the first quarter of next year, to inform Phase II pivotal trial design with a study anticipated to commence in the second quarter of next year.

Precedent Phase II pivotal trials with B-cell targeted cell therapies in LN or SLE and LN suggests that a relatively small single-arm pivotal study may suffice given the transformational clinical benefits observed with immune resetting cell therapies. Next slide, please.

The autoimmune program with ADI-001 is quite robust. We have seen a nice uptick in the number of sites interested in enrolling patients. We continue to enroll LN and SLE patients and recently also started enrolling systemic cirrhosis patients. We expect to enroll patients with RA in the very near future and also see interest from sites in enrolling patients with myositis and ANCA vasculitis.

ADI-212, our optimized next-generation gene-edited and armored clinical candidates designed to enhance potency in solid tumors and deliver multiple antitumor mechanism of action to the tumor microenvironment, ADI-212 is expected to enter the clinic in the first half of 2026. But today, we'll be focusing on the data from our Phase I trial in LN and SLE. Next slide, please.

Given the strength of the data we are sharing with you today, we expect our ADI-001 program to generate a number of meaningful milestones throughout 2026. We will review these milestones in more detail shortly.

With that, let me now turn the call to Julie to walk you through the clinical data in more details on the next slide.

Okay. Thank you, Chen. Good morning, everyone, and thank you for joining us. I am pleased to be here today to share these preliminary results from the Phase I study of ADI-001 in patients with LN, Lupus Nephritis; and SLE, Systemic Lupus Erythematosus.

This slide here just summarizes the data that I'll be showing you today. It includes seven patients in total, five LN and two SLE as of August 31 data cut.

I'm very pleased to report that we saw a rapid and sustained reduction in the SLEDAI-2K and PGA scores across all patients. You will also see that all LN patients had a reduction in proteinuria. Three patients achieved a complete renal response or CRR. These same three patients also achieved DORIS remission. The other two patients fit the protocol definition of a partial renal response or PRR, which is defined as a drop in proteinuria by greater than 50% from baseline.

ADI-001 was very well tolerated with no CRS greater than Grade 1, no ICANS and only one Grade 1 infection. There was clear evidence of an immune reset that Blake will walk you through in a bit. And all patients discontinued immunosuppressants and tapered steroids to zero or below 5 milli equivalents of prednisone daily.

So next slide, please. In the interest of time, I'm not going to go into great detail on this slide other than to remind you that there is a major unmet medical need for LN and SLE. Most patients get treated with chronic triple therapy that is two immunosuppressants and a steroid. More recently, there is even a suggestion of adding on a biologic treatment. All these therapies carry significant toxicities in these young patients. There is a clear need for a onetime therapy with a favorable safety profile that can deliver flare-free remissions without the need for these chronic therapies.

Next slide, please. Here's a quick review of our trial design. This is a Phase I study with a 3+3 basket design, which includes several autoimmune indications that you can see on the bottom left of this slide and then a dose expansion that is indicated on the bottom right. The patient's journey begins with signing consent, a screening period, conditioning regimen, cell infusion, a 28-day DLT dose-limiting toxicity evaluation period and then follow up. Patients are considered enrolled when they start conditioning.

Next slide, please. Primary endpoints for Phase I studies are always safety and tolerability, and our study is no exception. Secondary and exploratory endpoints focus on pharmacodynamic endpoints, including B-cell depletion, reconstitution and immune reset and the clinical efficacy endpoints are specific to each disease as outlined on the bottom right of this slide.

Next slide, please. Well, this is the baseline characteristics of all five LN patients and two SLE. They have follow-up ranging from 2 to 9 months, you can see they're primarily young women that have been living with their disease for quite some time, ranging from 2 to 22 years, and this reflects the typical demographics for SLE and LN.

Their baseline SLEDAI scores were in the mid-teens, and all LN patients had over 1.5 grams of protein in their urine. Patients had anywhere from three to seven prior therapies, and overall, these patient baseline characteristics are consistent with other data sets from company-sponsored clinical trials with B-cell depleting autologous cell therapies.

Let's go to the next slide, please.

So let's look at safety. ADI-001 was extremely well tolerated in these patients with no SAEs reported, no ICANS, and no CRS events greater than Grade 1. We had two patients with Grade 1 CRS, which, of course, is defined by the American Society of Transplantation and Cellular Therapy as a fever of over 38 degrees centigrade, which is about 100.4 degrees Fahrenheit. We also had one patient with a Grade 1 upper respiratory tract infection that happened about 3 months after cell infusion and resolved quickly without the need for antibiotics. Most notably, we did not have any neurotoxicity, no ICANS, no HLH, no GvHD.

Let's go to the next slide to see how ADI-001 data compares to other therapies in development.

So you could see in the blue box on the left, ADI-001 safety profile compares favorably with autologous alpha-beta CAR-T therapies in autoimmune patients. We believe this profile gives us the potential opportunity to dose ADI-001, as an off-the-shelf product in the outpatient setting. We were so encouraged by these results that we plan to speak to the FDA to see if we could administer ADI-001 as an outpatient therapy in clinical trials going forward. This would be a huge win for patients in our studies. And if approved, it will eliminate a major burden on the healthcare system by making this therapy more readily available. So please stay tuned for more information on that.

Let's move on to the next slide, please.

This slide shows the efficacy data for our LN patients specifically. You could see all five LN patients that received ADI-001, achieved a renal response. That's a wonderful outcome. In the bright blue, you can see three complete renal responses and DORIS remissions for patients LN1, LN4 and LN5. Two LN patients achieved a partial renal response, which is defined per protocol as a drop in proteinuria by more than 50% from baseline.

As far as we know, all these responses are ongoing at this time. We're also pleased to observe that the complete renal response rate shown here exceeds 40%. 40% is what regulatory authorities have signaled to other companies as a bar for success for a single-arm pivotal study for cell therapies in lupus nephritis.

Let's go to the next slide, please.

Well, this is a summary of all the SLEDAI-2000 -- SLEDAI-2K scores for all patients. We're extremely pleased to see that patients had a brisk and durable reduction in their symptoms as defined by the SLEDAI. You can see SLEDAI scores from these patients start out in the mid-teens and have a nice decline.

If you draw your attention to the orange triangle on LN1, LN4 and LN5, these are the patients that achieved a complete renal response and are also in a DORIS remission. The asterisk on this slide highlights three patients that were missing biomarker data, either anti double-strand DNA antibodies or complement levels at these particular visits. So we just assumed that they were positive to show the most conservative data for the SLEDAI-2K.

All right. Next slide, please.

This shows the PGA scores. This slide shows a rapid and sustained reduction in the Physician Global Assessment, or PGA, across all patients, which further highlights ADI-001's impact on overall disease activity. The bright blue line that you see represents the mean PGA for all patients. If you draw your attention for a moment for this orange line, mustard color, you will see the data for patient SLE-2. You could see that their PGA score decreased from 2 to 0.6 by month 3.

On the last slide, I showed you that the same SLE-2 patient had a clinical SLEDAI score of 0. So it's kind of important to highlight that this patient missed the DORIS remission cutoff by 0.1. And we're anxiously awaiting for this patient's next visit to see if they become a DORIS remission if all continues.

Next slide, please.

All patients discontinued immunosuppressants. And you see on this slide that all patients tapered their steroid use to zero or below physiologic levels, which is considered 5 milli equivalents of prednisone daily. Four of seven patients discontinued all steroids, and the remaining three tapered their steroids to 5 milli equivalent or less of pred. This is a tremendous result for patients given that current therapy includes chronic treatment with immunosuppressants and steroids that are associated with significant toxicity.

Long-term corticosteroid use, of course, leads to cataracts, diabetes, bone loss, easy bleeding, not to mention psychological issues. These treatments negatively impact quality of life for patients and their ability to live independent lives.

In summary, we're very excited with this data set. Patients want a single treatment with minimal side effects that could lead to disease remission and prevention of organ damage. We will continue to follow these patients enroll additional LN and SLE patients on the study and of course, advanced enrollment in all other cohorts.

And with that, I'm going to turn it over to Blake to summarize the data in immune reset. Blake?

Thanks, Julie. Let's go to the next slide, please. These robust clinical responses are particularly compelling and are further supported by biomarker evidence of an immune reset. We see multiple levels of evidence supporting this reset. With the loss of B-cell clones presenting at baseline and the emergence of a new less antigen-experienced B-cell repertoire. Specifically, we saw evidence of deep and broad B-cell depletion. That is the first step in a reset. Then we saw reconstitution driven primarily by naive and non-class switched B-cells.

At the genetic level, we also observed depletion of clonally dominant and potentially pathogenic B-cell receptor clones. This was followed by the emergence of a new B-cell repertoire associated with previously undetected antigen receptor sequences. So we've checked the box here on all of these.

Let's now go to the data and take a closer look. Next slide, please.

Looking generally at B-cell depletion, we can see that every patient experienced a deep and broad B-cell depletion, all with multiple time points where B cells were undetectable in the first month after treatment. This initial period of deep depletion was followed by reemergence of B cells within a 1- to 4-month window. This is very much in line with the dynamic seen with autologous CD19 CAR-Ts. With ADI-001, we are clearing the field and allowing new graphs to grow.

Next slide.

This slide provides an initial look at what these shoots are like with respect to B-cell phenotype and the degree of antigen experience associated with those B cells. Here, we show the spectrum of B-cell experience and maturation ordered from left to right, starting with the less antigen-experienced naive B-cell on the left and running through the most antigen experienced plasmablasts on the far right.

Here, we see that the reconstitution of B cells was primarily driven by naive, transitional, and non-class switched B cells, which is exactly what we want to see. And this is again in line with what has been previously seen with autologous CD19 CAR-Ts. These data are consistent with the current level of definition of an immune reset as reported by others. However, this doesn't objectively tell us about how these B cells are engaging with their antigens. To get a more objective view of this, we turn to deep sequencing of B-cell receptors which is how these cells recognize and engage auto-antigens.

Let's go to the next slide.

This slide shows our insights from deep sequencing in three patients from whom samples are available and demonstrate that dominant B-cell receptor clones that were seen at baseline were broadly eliminated after treatment with ADI-001, and were largely not detectable in reemerging B cells. Sorted from top to bottom are dominant B-cell clones, each expressing a unique B-cell receptor and the relative abundance of these clones is depicted by the depth of color.

In the right column for each of these patients, we see that these clones were broadly eliminated in B cells that reemerge at the 6-month and 3-month time points following treatment with ADI-001. Using deep sequencing, we can see that we are clearing the field and initiating an immune reset at the B-cell receptor level at the level where these cells engage with antigens. We can use this same analysis to evaluate whether the grass that grows in its place is in fact new.

Let's go to that in the next slide.

Here, we expand the view of it, looking again at the dominant B-cell receptor seen at baseline, now shown in pink for each of these patients. Following these tracks, we can see that these were largely eliminated and no longer detectable in B cells reemerging following treatment with ADI-001.

Similarly, in blue, we have highlighted B-cell receptor sequences that were not detected or present at baseline. We can see that these patients' B-cell repertoires are largely repopulating with completely novel B-cell receptor sequences, suggesting that these patients have experienced an immune reset at the antigen receptor level, representing a new B-cell repertoire. This depth of view for the immune reset is very much a story of out with the old and in with the new.

Let me pass it back to Chen.

Thanks, Blake. Next slide, please. This slide shows the sustained reductions in SLEDAI scores across industry-sponsored clinical trials with autologous CD19 alpha-beta cell therapies.

As you can appreciate, the sustained reduction in SLEDAI with ADI-001, is overall consistent with these data. Importantly, obe-cel on the top right observed three CRRs out of six LN patients or a 50% complete renal response rate. Rap-cel on the top middle chart presented a very robust data set at EULAR just a few months ago. The data set included 12 LM patients and nine SLE patients. And on the next slide, we can see the percentage of patients that resolved that proteinuria.

Next slide, please.

As you can see on the top right of this slide, the percent of patients with proteinuria dropped from approximately 70% at screening to 35% by month 12, suggesting approximately a 50% complete renal response rate. So we have two examples of company-sponsored clinical studies with autologous CD19 alpha-beta CAR-T in LN patients demonstrating an approximately 50% complete renal response rate. And these data are very consistent with the CRR rate we are observing with ADI-001. ADI-001 has the advantage of being off the shelf and generally well tolerated, hence potentially optimal for dosing in an outpatient setting.

Next slide, please. As Julie mentioned earlier, regulatory authorities have signaled to other companies that the bar for success in single-arm pivotal studies with cell therapies in LN is a complete renal response rate of 40%. This slide shows the pivotal studies underway in LN and SLE and LN with autologous CD19 alpha-beta CAR-T product candidates.

Let's go to the next slide. There are two key takeaways from the data we presented today. One, this clinical data supports the potential of ADI-001, as an off-the-shelf immune resetting, onetime, well-tolerated therapy that could be used in the outpatient setting. And two, we believe that a product candidate with this product profile could enable treating physicians to provide patients with LN or SLE with a potential of onetime therapy that leads to disease remission or how disease progression, while patients discontinue the use of chronic immunosuppressants and reduce the dose of corticosteroids to zero or below physiological levels. This could be a transformational treatment for many patients with autoimmune diseases.

Next slide, please. We have now activated over 25 clinical sites globally, which is a testament to our team's focus and excellent execution as well as demonstrating investigators' interest in ADI-001. The pace of enrollment, we are now observing reinforces our confidence in our timelines for future milestones.

Next slide, please. We believe there is a significant market opportunity in front of us and that ADI-001 has the potential to change clinical practice across multiple autoimmune indications. In addition to the six indications we already have underway in our Phase I program, we have recently opened enrollment for a new Phase I study for the treatment of RA. This trial will explore the use of ADI-001, following Cy/Flu versus Cy only conditioning. With these trials underway, we are poised for a number of milestones in 2026, as outlined on the next slide.

We plan to request a meeting with the FDA in the first quarter of 2026 to inform Phase II pivotal trial design in LN or in LN and SLE, with the study anticipated to commence in the second quarter of 2026. Precedent Phase II pivotal trials with B-cell targeted cell therapies suggest that the relatively small single-arm pivotal study may suffice given the transformational clinical benefits observed with immune resetting cell therapies. Stay tuned for these updates. SLE and LN patient enrollment to the ongoing Phase I is expected to continue until the Phase II pivotal study is open for enrollment. The Phase I program is now open for enrollment of patients with Systemic Cirrhosis, Myositis, Stiff Person syndrome, ANCA vasculitis, and RA. We expect 2026 to be a year with many meaningful milestones.

In the first half of 2026, we expect the following milestones. A clinical update in SLE and LN with more patients enrolled to our Phase I study and longer follow-up. We expect to announce alignment with the FDA on the pivotal study design in LN or in LN and SLE. We expect to announce the initiation of a pivotal study in LN or LN and SLE. We expect a clinical update in systemic sclerosis and a potential clinical update in other autoimmune indications.

In the second half of 2026, we expect to provide the following milestones. A clinical update in SLE and LN, a clinical update in systemic cirrhosis, clinical data from our study in RA, that we recently opened for enrollment, and a potential clinical update in other autoimmune indications. We also have an ongoing program with ADI-212 in metastatic prostate cancer. We plan to file an IND for the program in the first quarter and clinical clinical data potentially in the second half of next year.

With that, let's open the call for Q&A. Operator?

[Operator Instructions] Our first question will come from Jenna Li with Jefferies.

This is Jenna joining for Clara at Jefferies. Congrats on this data. We have two questions, if we may. The first one is, can you help us understand if there were any notable trend in LN2 and LN3, both of which had complete B-cell depletion. Are you observing anything that could suggest they may advance towards complete remission with longer follow-up? And specifically on the SLEDAI chart, I noticed that for both of these patients, the last month had a start on it, and it looks like there were some unavailable samples and some assumptions. If you could just elaborate on that and how that could change or evolve over time?

Sure. Let me start and then perhaps Julie can add. So first of all, what success looks like, if we -- in 50% of the patients, if we can see a complete renal response and they stop taking their immunosuppressants and reduce corticosteroids to zero or below 5 milli equivalent of prednisone, that's a huge win. Keep in mind that otherwise, these patients will continue to be immunosuppressed and tend to die in their 50s from kidney failure. So that's a big, big win.

Regarding the question of LN2 and LN3, Julie, perhaps you can share some background. I think patient 2 had many years of disease, if I recall.

Yes. And thank you. That is correct. Patient 2 had disease for 22 years. She's our longest duration. These two patients are the ones that had a partial renal response, that decreased their proteinuria by greater than 50%. As Chen said, this is still a major win for them that they're off immunosuppressants and off steroids or nearly off steroids with less than 5 milli equivalents.

And you had in the -- there was a second question. Can you remind us what was the second question?

Asterisk. Yes, essentially -- so for example, LN2 and LN3, we just wanted to get you guys there best update as of August 31. So for example, for LN2 and LN3, we brought them to unscheduled visit. And in that unscheduled visits, we got their clinical fleet, but we didn't have the sample to analyze for dsDNA or for C3 and C4. So we just assume they're positive for the most conservative view of the SLEDAI-2K score.

Okay. Got it. And if I may, how would this data inform your thinking on next steps? Potential design for registrational patient selection, baseline, dose, et cetera.

Yes, absolutely. They say, the work of the holy ones is done by others. So first of all, other companies like BMS or Autolus or Novartis have moved to potentially pivotal studies after data sets along the number of patients that we provided, the same duration of follow-up. What we know based -- there was a slide here in the deck. What we know is that these studies tend to be single arm, number of patients in the 30 to 90 patients, and the endpoint is a complete renal response and the bar is at least 40%.

So what's the design? It's kind of out there and we expect to follow what the others have established in the field. The only question that we have is the pivotal design in LN or in LN and SLE or maybe start with an LN and then expand to an LN and SLE, and we'll discuss this with the FDA in the first quarter of next year.

In the interest of time, please limit to one question. Our next question will come from Yatin Suneja with Guggenheim.

Perfect. Julie and Chen, thank you so much for the presentation. Excellent results here. Obviously, very impressive in terms of both efficacy and safety. So the question I have is around durability. Could you maybe talk about your view on the durability? How should we think about that, maybe contextualize some of the immune reset results that you are seeing in that regard? So that's sort of first question.

And then the second, which is a quick question is, could you just let us know what was the lymphodepletion doses that you use? Was it similar to what we are seeing with other CAR-T auto designs?

Sure, absolutely. We're very happy with the durability. What's nice to see is generally immune resetting therapies show very nice durability. So as you can see, just as an example, LN1 had a complete trailer response at month 1 and has a follow-up of 9 months. Generally, all the patients as of August 31, we've seen very nice responses. I can confirm to you that as of now, we're not aware of any relapse. And if we're aware of anything, then patients continue to improve. So we're very, very happy with what we're seeing here.

The data in terms of the number of patients and follow-up of patients is completely consistent with what autologous cell therapy companies had before they started their pivotal studies.

So that was one question, and you had another question, lymphodepletion. The lymphodepletion regimen here is very consistent with autologous cell therapies that are going into pivotal studies. There is nothing unique about it.

Our next question will come from Asthika Goonewardene with Truist.

This is Karina for Asthika. Congrats on the data. I guess, you mentioned like on baseline characteristics, but how would you compare the baselines to other LN trials? And I guess more specifically, is it more similar to George Schett's baseline characteristics?

Absolutely. First of all, thank you for asking. What we're not comparing, we're not comparing to baseline characteristics of a ISTs. What we are comparing is generally to baseline characteristics of other company-sponsored studies. But even if compared to Schett, it might be the same.

Overall, when you look at the age, it's approximately the same. If you look at the duration of disease, 2 to 22 years is very much the same. If you look at the SLEDAI score, our mean was 14. If you look at Novartis, which is the largest industry-sponsored study that was presented so far, their mean SLEDAI at screening was, guess what, 14. If you look at the UPCR, above 1.5. This is definitely an LN patient. We confirmed all LN patients with a recent biopsy. If you look at the number of prior line of therapies, 3 to 7 is very consistent with other studies.

And if you look at the corticosteroid levels, they all were on steroids. So bottom line, if you compare our data set to the data set presented by small companies like BMS or Novartis, and also Autolus very consistent with their data set. If you look at our SLEDAI reduction, very consistent. If you look at the baseline characteristics, very consistent. And if you look at the complete renal response very consistent. So we're very happy with this data.

Okay. That's helpful. And I guess another one is regarding pivotal study. Would this potentially be single-arm similar to obe-cel and BMS? Or how are you thinking about the pivotal design?

Again, can you repeat the question? I just want to make I understand it.

Yes. On the pivotal design, are you thinking about doing potentially a single-arm study similar to Autolus and BMS? Or how are you thinking about the design?

Yes, absolutely. So we know that the clinical benefit that we see with these studies are so transformational that the pivotal study this year are expected to be single arm, relatively small with an endpoint that's relatively short in the 6-month range and the endpoint is complete real response or it might be, in some cases, it might be dose remission if it includes SLE. Yes, absolutely. We expect relatively small single-arm pivotal study, and we'll discuss this with the FDA in the first quarter of next year and hopefully start the study in the second quarter.

Absolutely. The range is approximately 30 to 90 patients based on what we've seen from other companies.

Our next question will come from John Newman with Canaccord Genuity.

Congrats on the tremendous amount of hard work that you guys have put in to this study and all the programs. This is a really great day for lupus patients and autoimmune patients. Just had two quick questions. So just following on to one of the earlier questions, we saw with Novartis' data for rapcabtagene, they saw a very rapid decline in a lot of the SLEDAI-2K items, including proteinuria. And importantly, that proteinuria, even though it didn't go to zero, it continued to drop over time. So my question is, is it reasonable to expect that in patients, I believe LN2 and LN3, we could still continue to see some improvement in terms of the proteinuria as patients continue to be followed?

Yes. Let me try to address it, and if Julie has something to add, that's great. So keep in mind that gamma delta-1 T-cells have tissue tropism, including the kidneys. By the way, we did confirm this in our RCC study with a different gamma-delta 1 cell therapy, where we saw significant exposure in the kidney.

What does that mean? If you look actually at Novartis' data set, they saw a 50% reduction in the patient -- in the percent of patients with proteinuria at month 12. What we saw three out of five, i.e., 60% of the patients with complete renal response at month 6. So this only may suggest that patients might get better sooner on the Lupus Nephritis components. So we're very, very happy with that. Regarding the continued improvement in the kidney function, it's something that we have seen and I can tell you that today, all the responses are ongoing or even getting better.

The other point I might mention to you, there was one slide that we presented that show the RAxul data. I discussed the right side of the slide, where I show this 50% reduction in proteinuria. I want to point your attention to the left side of this slide, where actually Novartis outlined in blue, the reduction of SLEDAI in the SLE patient. And in green, the reduction in SLEDAI in the LN patients. And as you can see, the reduction in the LN patients, there is like a little bit of a plateau around 4. And based on the data that we see, you can see that this is a more persistent proteinuria. So overall, our data compare very well to Novartis, if only maybe you see a faster resolution of the proteinuria in patients. Great question, John.

And then, just one quick follow-up question. Can you comment on how you taper the immunosuppressant before treatment with auto cell. And also importantly, how does this compare to an autologous CAR-T where patients may be off of immunosuppression, may need to be off of immunosuppression during manufacturing. Just in terms of ease of use for both the patient and the physician.

Yes, yes. Let me walk me through the journey, because it's very different. So generally, with autologous cell therapies, you want patients to discontinue immunosuppressants, let's say, a month before the leukapheresis, because you want to get their cells with good fitness. So you stop immunosuppressants for a month, then you need to schedule a leukophoresis chair and fight for the resources in the hospital, because there's not a lot of leukophoresis chairs in terms of capacity. Then you get the leukophoresis. Then you wait approximately a month before starting the treatment. So the patient needs to be for approximately 2 months of immunosuppressants before they start the study.

Then you need to schedule time with HemOnc, because these are autologous alpha-beta T-cells and you never know who's going to get the high-grade ICANS, right? It's -- you just never know. We see these events of Grade 3 and Grade 4 ICANS with autologous cell therapies. So they need to get resources from HemOnc to really watch over these patients and manage all of their toxicities.

In our case, it's very simple. Patients get into screening. Screening is 28 days during the screening that take off their immunosuppressants. And then, they come and after 3 days of conditioning, they get a single dose of ADI-001, and it's very well tolerated, very well tolerated. No ICANS and just two cases of CRS, which were just Grade 1 and simple fever. So very, very different. In our case, you just stop immunosuppressants during screening and started treatment. Much, much, much, simpler for the patient and for the treating physician.

Your next question will come from Robert Driscoll with Wedbush.

Some really nice data here. I just wondering if there is a way to kind of characterize which patients may have more severe existing kidney damage at baseline just in terms of maybe predicting which of those kind of lupus nephritis patients kind of may have those more persistent proteinuria scores following treatment?

Julie, any feedback you can provide here? I think the field is really young in trying to define who will respond and who will not.

Yes, I tend to agree in clinical practice, when you do biopsies, you look at chronicity and activity scores, but none of that has panned out to really correlate exactly with outcome.

Yes. But Robert, I would just add to you, having three CRRs out of five is amazing, but also two -- if two of the patients are at partial renal response, it's also great, because keep in mind dose immunosuppressants and corticosteroids have such significant toxicities. And in many cases, patients with LN die in their 50s. In many cases, because of an infection, because they have been immunosuppressed for decades. So if you can give them one treatment and only halt the disease progression, and they stop taking these chronic immunosuppressants and high-dose steroids, that's still an amazing outcome, like we want to prevent disease progression and further organ damage in these patients.

So even if you can predict who is going to be a partial renal response still, it's great help for these patients to be able to stop their chronic immunosuppressants and steroids.

Yes. That makes sense. And then, maybe just sneak one more in. Just on the dose going forward. Just how are you thinking about that?

Sure. So we're very, very happy with the efficacy that we're seeing and the safety per protocol. We're increasing the dose to 1e9. We already started dosing the 1e9 dose. But based on the data so far, we expect a recommended Phase II dose to be 3e8. We can see us improving efficacy more. This is as good as it gets when you compare it to all the autologous cell therapies. So that's currently what we expected to recommend Phase II dose of 3e8.

Your next question will come from Reni Benjamin with Citizens JMP.

Congratulations Chen and team on the data. A couple of questions for you, I guess. One, any thoughts on potential re-dosing of these patients, especially the partial renal responses? And as you think about the 25 sites that are now activated and kind of the current enrollment trends, as we think about the next update that's coming in the first half of '26, how many more patients do you think we might see?

And in terms of durability, what do you think is the kind of durable response rate?

Reni, you got to stop. You asked three questions. So let's go one by one. So the first one, can you repeat? Let's just go one by one.

Yes. Any thoughts on redosing?

No. We don't have right now any thoughts about redosing. This is single-dose treatment, and it produced great data so far. We certainly have the ability to redose. This is an off-the-shelf product and there is no prevention for people to redose in the future. But right now, this protocol is a single administration. So that was one question.

And then, the next question was regarding site. So currently, we have -- we actually have more interest for more sites that are interested in joining the study. So we expect to continue to increase the number of sites. We see increased enrollment -- increased interest in enrollment to the study patients -- or sorry, investigators that provided one patient to the study, very quickly come with their second patient with LN or SLE or with patients with systemic cirrhosis and now we see patients interested with myositis and ANCA vasculitis. So this process, once you have a drug that's off-the-shelf well tolerated and provides these type of efficacy, it just kind of fit itself and you see more and more interest from patients and from physicians and from sites.

So we're actually very optimistic about the pace of enrollment here. I can say that, if you told me that the three patients per month, let's put it this way as of now, enrolling three patients per month wouldn't be something that wouldn't be normal for the company, but we have not guided for how many patients will have in the first half of next year update. But I would -- I believe that this data that we're presenting today de-risks the pivotal study in a very significant way.

And next -- in the first half of next year, following the discussion with the FDA and the additional patients that will present the pivotal study will be completely de-risked, but we'll see that in the very near future. That was your second question, and there was a third, if I remember.

Yes. Thanks. As we think about the competitive landscape, the fact that there are registrational studies, kind of, ongoing right now. How do you see 001, maybe threading that needle in a world, right, not just for clinical execution, but in a world where, let's say, there's multiple cell therapies approved, right, in something like LN?

Reni, we don't need to thread the needle. Because the tolerability that we see here should enable us to dose in outpatient settings. This opens the universe to so many sites that are interested in joining these studies, but just so far, don't have the capabilities, because they don't have the leukophoresis bed and they don't know how to manage these CRS and ICAN. So from a clinical execution, we see a great potential.

In clinical practice, we would expect the same advantage to continue, because if you're a patient, why would you stop immunosuppressants for 2 months and you might flare, then do the leukophoresis and then be concerned about CRS and ICANS. If you can just take something that's available off-the-shelf and is safer and doesn't require all the hassle around the total cell therapy. So we believe that this actually positions us for great success with an off-the-shelf and differentiated product.

Your next question will come from Soumit Roy with Jones Trading.

Congrats on durable data, especially the robust immune reset. A quick one on the CRR EGFR definition. Is it going to be in line with Cabaletta autologous type cell therapy names where greater than 60 ml per minute? Or is it are Roche and GSK, they are doing it at 85 to 90 ml per minute. Is that something still up in the air and needs to be sorted out with the FDA?

No, I don't think so, and Julie might correct me here. The complete renal response, that definition that we're using is the one that's applicable for pivotal studies essentially proteinuria needs to go to below 0.5. And EGFR needs to be stable, i.e., don't want to see a reduction of more than 15% in the EGFR. That's the definition in pivotal studies. That's a definition that we're using. And separately, EGFR above 60 is considered in the normal range, but that's unrelated to the definition of complete renal response.

Julie, anything that you would correct here?

No, that's absolutely correct. Everything above 60 is normal.

Got it. One quick one is the dose levels for the patients 2 and 3. If you can remind us, was this 3 million? Or was it lower versus 1, 4 and 5 patients?

Yes. It's actually on the first slide, the dose for the first 3 patients with LN was 1e8, that's 100 million CAR-T cells, and the dose for the next 2 patients was 3e8, which is 300 million CAR-T cells.

Our final question will come from Robert Burns with H.C. Wainwright.

Congrats on the data. Just one for me, if I may. So given the strength of this data set as well as the allogeneic differentiation or 001 relative to the autologous competitors, how are you thinking about potential BD opportunities for 001, both in the U.S. as well as ex U.S.?

Yes Absolutely, Robert. Well, certainly, I can tell you that there is generally interest in BD, but we're going to be opportunistic. When it comes to BD, we absolutely want to make sure we maximize shareholders' value. We believe that the valuation of the company and that's reflected in the program right now is completely not in even remotely even close to the ZIP code where it should be, but we'll be listening to BD opportunities. But again, we want to execute, build value and generate the right returns for patients and progress aggressively with this program. We have the sites engaged. We have more sites engaged, we know what a pivotal study looks like. We can execute on a pivotal study. So Robert, we want to run.

Awesome. I love hearing that. Thank you guys.

We have reached the top of the hour. This concludes today's call. Thank you for joining us, and goodbye.